Transgenic mice have been developed recently that contain copies of the well-defined mutagenesis reporter gene, lacI, in an integrated bacteriophage-based shuttle vector. The lacI gene, which is present in all cells of the mouse, can be excised specifically from isolated genomic DNA and efficiently packaged into bacteriophage particles after the addition of packaging extracts. Mutations of the lacI gene are easily detected by the derepression of beta-galactosidase resulting in blue plaques in the presence of X-gal. Originally developed as a short-term in vivo mutagenesis assay to screen genotoxic agents, we have used this system to measure naturally occurring DNA mutations as a function of chronological age. There was a linear increase in the presence of phenotypic lacI mutants from birth to 24 months (r = 0.731, P < 0.001), such that 24-month-old mice have accumulated approximately fourfold more mutants than newborn pups. Molecular analysis of these spontaneously arising DNA mutations showed them to result predominantly from base substitutions (80.6-98.5%) that were equally distributed between transitions and transversions. However, lacI mutations in animals > 3 months of age demonstrated a higher percentage of mutations (12-19.4% vs. 1.2%) resulting from discriminable size changes (> 20 bp) than was observed for mice 1-2 months old. Sequence analysis of mutations resulting from a > 20 bp size change revealed them to be due to a duplication of adjacent lacI sequence. These results indicate that there is a gradual accumulation of DNA mutations with age and that the types of mutations also are influenced by the age of the animal.

Congenital malformations are the leading cause of death in infants of insulin-dependent diabetic mothers. Although there are data to suggest that hyperglycemia itself is teratogenic, few mechanisms have been proposed to explain diabetic embryopathy. To address the possibility that DNA mutations play a role in the fetal malformations associated with diabetes, we developed a transgenic mouse model system to measure the mutation frequency of a neutral target gene, lacI, during embryonic development in a maternal hyperglycemic environment. Despite the short 21-day gestational period of the mouse, we observed a twofold increase in the mutant frequency of the lacI transgene in fetuses that developed in a mild diabetic environment (blood glucose > 8.3 mmol/l) compared with those that developed under normoglycemic conditions (blood glucose < 8.3 mmol/l). These data provide the first direct evidence of the genotoxic effect of diabetes in vivo and suggest a mechanism for the teratogenicity of the maternal diabetic environment.

A great change in education is taking place at this moment. Studies have shown our U.S. students to be behind, threatening our place in the global community. Our businesses decry the skills (or lack of skills) for their incoming employees. Everyone agrees that we need to change the tide. STEM is the current model holding everyone's attention, and the addition of the arts is gathering STEAM. Stakeholders weighing in to the debate seem to cause more confusion about what these terms mean, and how we can best implement them in the schools. This paper explores the role of the arts in the K-12 setting, and Middle School General Music in particular, and the impact it has as an integrating force in the STEM debate.

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